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IUCrJ Jul 2024The manuscript `Modeling a unit cell: crystallographic refinement procedure using the biomolecular MD simulation platform Amber' presents a novel protein structure...
The manuscript `Modeling a unit cell: crystallographic refinement procedure using the biomolecular MD simulation platform Amber' presents a novel protein structure refinement method claimed to offer improvements over traditional techniques like Refmac5 and Phenix. Our re-evaluation suggests that while the new method provides improvements, traditional methods achieve comparable results with less computational effort.
Topics: Proteins; Molecular Dynamics Simulation; Crystallography, X-Ray; Protein Conformation; Macromolecular Substances; Software; Models, Molecular
PubMed: 38958017
DOI: 10.1107/S2052252524005803 -
IUCrJ Jul 2024A series of events underscoring the significant advancements in micro-crystallization and in vivo crystallography were held during the 26th IUCr Congress in Melbourne,... (Review)
Review
A series of events underscoring the significant advancements in micro-crystallization and in vivo crystallography were held during the 26th IUCr Congress in Melbourne, positioning microcrystallography as a pivotal field within structural biology. Through collaborative discussions and the sharing of innovative methodologies, these sessions outlined frontier approaches in macromolecular crystallography. This review provides an overview of this rapidly moving field in light of the rich dialogues and forward-thinking proposals explored during the congress workshop and microsymposium. These advances in microcrystallography shed light on the potential to reshape current research paradigms and enhance our comprehension of biological mechanisms at the molecular scale.
Topics: Crystallization; Crystallography, X-Ray; Crystallography; Macromolecular Substances
PubMed: 38958014
DOI: 10.1107/S205225252400513X -
Development (Cambridge, England) Jul 2024Transcription initiates at the core promoter, which contains distinct core promoter elements. Here, we highlight the complexity of transcriptional regulation by...
Transcription initiates at the core promoter, which contains distinct core promoter elements. Here, we highlight the complexity of transcriptional regulation by outlining the effect of core promoter-dependent regulation on embryonic development and the proper function of an organism. We demonstrate in vivo the importance of the downstream core promoter element (DPE) in complex heart formation in Drosophila. Pioneering a novel approach utilizing both CRISPR and nascent transcriptomics, we show the effects of mutating a single core promoter element within the natural context. Specifically, we targeted the downstream core promoter element (DPE) of the endogenous tin gene, encoding the Tinman transcription factor, a homologue of human NKX2-5 associated with congenital heart diseases. The 7bp substitution mutation results in massive perturbation of the Tinman regulatory network orchestrating dorsal musculature, manifested as physiological and anatomical changes in the cardiac system, impaired specific activity features and significantly compromised viability of adult flies. Thus, a single motif can have a critical impact on embryogenesis and, in the case of DPE, functional heart formation.
PubMed: 38958007
DOI: 10.1242/dev.202355 -
Journal of Experimental Botany Jul 2024
PubMed: 38957989
DOI: 10.1093/jxb/erae292 -
Arteriosclerosis, Thrombosis, and... Jul 2024Institutional support is crucial for the successful career advancement of all faculty but in particular those who are women. Evolving from the past, in which gender... (Review)
Review
Institutional support is crucial for the successful career advancement of all faculty but in particular those who are women. Evolving from the past, in which gender disparities were prevalent in many institutions, recent decades have witnessed significant progress in supporting the career advancement of women faculty in science and academic medicine. However, continued advancement is necessary as previously unrecognized needs and new opportunities for improvement emerge. To identify the needs, opportunities, and potential challenges encountered by women faculty, the Women's Leadership Committee of the Arteriosclerosis, Thrombosis, and Vascular Biology Council developed an initiative termed GROWTH (Generating Resources and Opportunities for Women in Technology and Health). The committee designed a survey questionnaire and interviewed 19 leaders with roles and responsibilities in faculty development from a total of 12 institutions across various regions of the United States. The results were compiled, analyzed, and discussed. Based on our interviews and analyses, we present the current status of these representative institutions in supporting faculty development, highlighting efforts specific to women faculty. Through the experiences, insights, and vision of these leaders, we identified success stories, challenges, and future priorities. Our article provides a primer and a snapshot of institutional efforts to support the advancement of women faculty. Importantly, this article can serve as a reference and resource for academic entities seeking ideas to gauge their commitment level to women faculty and to implement new initiatives. Additionally, this article can provide guidance and strategies for women faculty as they seek support and resources from their current or prospective institutions when pursuing new career opportunities.
PubMed: 38957985
DOI: 10.1161/ATVBAHA.124.320910 -
Regenerative Medicine Jul 2024Adjunctive pharmacological treatment may improve nerve regeneration. We investigated nerve regeneration processes of PXL01 - a lactoferrin-derived peptide - after...
Adjunctive pharmacological treatment may improve nerve regeneration. We investigated nerve regeneration processes of PXL01 - a lactoferrin-derived peptide - after repair of the sciatic nerve in healthy Wistar rats. PXL01, sodium hyaluronate (carrier) or sodium chloride was administered around the repair. After 6 days axonal outgrowth, Schwann cell response, pan- (CD68) and pro-healing (CD206) macrophages in sciatic nerve, sensory neuronal response in dorsal root ganglia (DRG) and expression of heat shock protein 27 (HSP27) in sciatic nerves and DRGs were analyzed. Despite a lower number of pan-macrophages, other investigated variables in sciatic nerves or DRGs did not differ between the treatment groups. PLX01 applied locally inhibits inflammation through pan-macrophages in repaired sciatic nerves without any impact on nerve regeneration or pro-healing macrophages.
PubMed: 38957920
DOI: 10.1080/17460751.2024.2361515 -
ISME Communications Jan 2024Constitutive mixoplankton-plastid-bearing microbial eukaryotes capable of both phototrophy and phagotrophy-are ubiquitous in marine ecosystems and facilitate carbon...
Constitutive mixoplankton-plastid-bearing microbial eukaryotes capable of both phototrophy and phagotrophy-are ubiquitous in marine ecosystems and facilitate carbon transfer to higher trophic levels within aquatic food webs, which supports enhanced sinking carbon flux. However, the regulation of the relative contribution of photosynthesis and prey consumption remains poorly characterized. We investigated the transcriptional dynamics behind this phenotypic plasticity in the prasinophyte green alga Based on what is known of other mixoplankton species that cannot grow without photosynthesis (obligate phototrophs), we hypothesized that uses phagotrophy to circumvent the restrictions imposed on photosynthesis by nutrient depletion, to obtain nutrients from ingested prey, and to maintain photosynthetic carbon fixation. We observed an increase in feeding as a response to nutrient depletion, coinciding with an upregulation of expression for genes involved in essential steps of phagocytosis including prey recognition, adhesion and engulfment, transport and maturation of food vacuoles, and digestion. Unexpectedly, genes involved in the photosynthetic electron transfer chain, pigment biosynthesis, and carbon fixation were downregulated as feeding increased, implying an abatement of photosynthesis. Contrary to our original hypothesis, our results therefore suggest that depletion of inorganic nutrients triggered an alteration of trophic behavior from photosynthesis to phagotrophy in . While this behavior distinguishes from other groups of constitutive mixoplankton, its physiological response aligns with recent discoveries from natural microbial communities. These findings indicate that mixoplankton communities in nutrient-limited oceans can regulate photosynthesis against bacterivory based on nutrient availability.
PubMed: 38957873
DOI: 10.1093/ismeco/ycae083 -
Cureus Apr 2024The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact globally, resulting in a higher death toll and persistent health issues for survivors,...
Identification of Differentially Expressed Genes and Protein-Protein Interaction in Patients With COVID-19 and Diabetes Peripheral Neuropathy: A Bioinformatics and System Biology Approach.
The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact globally, resulting in a higher death toll and persistent health issues for survivors, particularly those with pre-existing medical conditions. Numerous studies have demonstrated a strong correlation between catastrophic COVID-19 results and diabetes. To gain deeper insights, we analysed the transcriptome dataset from COVID-19 and diabetic peripheral neuropathic patients. Using the R programming language, differentially expressed genes (DEGs) were identified and classified based on up and down regulations. The overlaps of DEGs were then explored between these groups. Functional annotation of those common DEGs was performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Bio-Planet, Reactome, and Wiki pathways. A protein-protein interaction (PPI) network was created with bioinformatics tools to understand molecular interactions. Through topological analysis of the PPI network, we determined hub gene modules and explored gene regulatory networks (GRN). Furthermore, the study extended to suggesting potential drug molecules for the identified mutual DEG based on the comprehensive analysis. These approaches may contribute to understanding the molecular intricacies of COVID-19 in diabetic peripheral neuropathy patients through insights into potential therapeutic interventions.
PubMed: 38957825
DOI: 10.7759/cureus.58548 -
Frontiers in Genetics 2024has been at the forefront of genetic studies and biochemical modeling for over a century. Yet, the functions of many genes are still unknown, mainly because no...
has been at the forefront of genetic studies and biochemical modeling for over a century. Yet, the functions of many genes are still unknown, mainly because no phenotypic data are available. Herein, we present the first evidence data regarding the particular molecular and other quantifiable phenotypes, such as viability and anatomical anomalies, induced by a novel insertional mutant allele of the gene. So far, the functions have only been theorized based on electronic annotation and presumptive associations inferred upon high-throughput proteomics or RNA sequencing experiments. The descendants of individuals harboring the allele were scored in order to assess mutant embryonic, larval, and pupal viability Canton Special (CantonS). Our results revealed that the homozygous / genotype determines significant lethality both at the inception of the larval stage and during pupal development. The very few imago escapers that either breach or fully exit the puparium exhibit specific eye depigmentation, wing abnormal unfolding, strong locomotor impairment with apparent spasmodic leg movements, and their maximum lifespan is shorter than 2 days. Using the quantitative real-time PCR (qRT-PCR) method, we found that is upregulated in male flies, but an unexpected gene upregulation was also detected in heterozygous mutants compared to wild-type flies, probably because of regulatory perturbations induced by the transposon. Our work provides the first phenotypic evidence for the essential role of , a scenario in accordance with the putative role of this gene in carbohydrate-binding processes.
PubMed: 38957808
DOI: 10.3389/fgene.2024.1355368 -
Frontiers in Health Services 2024The rapid detection and continuous surveillance of infectious diseases are important components of an effective public health response. However, establishing advanced...
The rapid detection and continuous surveillance of infectious diseases are important components of an effective public health response. However, establishing advanced molecular surveillance systems, crucial for monitoring and mitigating pandemics, poses significant challenges in resource-limited developing countries. In a collaborative effort, research institutions from Benin joined forces with Mali's National Institute of Public Health to implement a state-of-the-art molecular surveillance system in Mali. This approach was characterized by collaboration, multidisciplinarity, and tutoring. Key activities included a comprehensive assessment of infrastructure and human resources through document reviews, interviews, and laboratory visits; the development and validation of Standard Operating Procedures (SOPs) for advanced molecular surveillance following an inclusive approach; capacity-building initiatives for 25 biologists in Mali on sequencing techniques; and international tutoring sessions for eight Malian professionals held in Benin. These collective efforts enabled Mali to establish an advanced molecular surveillance system aligned with the WHO's global strategy for genomic surveillance. This manuscript aims to share experiences, insights, and outcomes from this initiative, with the hope of contributing to the broader discussion on strengthening global health security through collaborative approaches and capacity-building efforts, particularly in developing countries.
PubMed: 38957804
DOI: 10.3389/frhs.2024.1289394